febantel and Rodent-Diseases

Haemonchus contortus- and Trichostrongylus colubriformis-infected jirds (Meriones unguiculatus) are useful for anthelmintic studies. With concurrent infections of these parasites established in the jird, questions of not only anthelmintic activity, but to some extent spectrum, could be assessed in a single model system. This report outlines a model using immunosuppressed (0.02% hydrocortisone in feed) jirds concurrently infected with H. contortus and T. colubriformis. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of each species, treated per os on day 10 postinoculation (PI), and killed on day 13 PI. Stomachs and small intestines were removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Contents of both organs were examined using a stereomicroscope (15-45 x). Various standard anthelmintics were evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses comparable to those required for efficacy against these parasites in ruminants. This model, using worms of 2 genera living in distinct sites, allows preliminary evaluation of anthelmintic activity and spectrum for experimental compounds in a single cost- and resource-efficient experiment.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Benzimidazoles; Bithionol; Diethylcarbamazine; Gerbillinae; Guanidines; Haemonchiasis; Macrolides; Piperazine; Piperazines; Pyrantel Tartrate; Rodent Diseases; Trichostrongyloidiasis

The metabolism of febantel has been investigated in the rat and the sheep. The general pathway seems to be similar in both species: ten urinary metabolites are the result of cyclisation, oxidation and/or hydrolysis process. Using synthetic samples, the embryotoxic study of all individual metabolites has been performed in the rat. Unchanged febantel and two other metabolites are responsible for teratogenic effects. A four steps toxogenic pathway is described which finally leads to the ultimate known teratogen: methyl (5-(phenylsulfinyl)-1H-benzimidazole-2-yl) carbamate. Metabolic similarities with other anthelmintics and residual consequences are discussed.

Topics: Abnormalities, Drug-Induced; Animals; Anthelmintics; Chemical Phenomena; Chemistry; Female; Fetal Death; Guanidines; Pregnancy; Rats; Rats, Inbred Strains; Rodent Diseases; Sheep